Therapeutic development targeting B7H3 in the tumor microenvironment of ovarian cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18210
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Research Institute, Shiga Medical Center
• Principal Investigator: Murakami Ryusuke 滋賀県立総合病院(研究所), その他部局等, 医長 (40782363)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 腫瘍微小環境

Outline of Final Research Achievements

Ovarian cancer is not as effective as expected for PD-1 / PD-L1 inhibitory treatment. In this study, B7H3 (CD276),the same immune checkpoint family as PD-L1, is highly expressed in non-immune-reactive ovarian cancer with low PD-L1 and is negatively correlated with the IFNγ signature, which reflects tumor immunoreactivity. Focused on B7H3, in a mouse model of allogeneic ovarian cancer, tumor cell B7-H3 knockout (KO) suppressed tumor progression, decreased the number of M2 macrophages, and increased the number of IFNγ + CD8 + T cells. Expression of CCL2 was suppressed in the B7-H3 KO tumor cell line. Expression of B7H3 was shown to induce migration and differentiation of M2 macrophages via the CCL2-CCR2 pathway.

Free Research Field

卵巣癌

Academic Significance and Societal Importance of the Research Achievements

卵巣癌ではB7H3が高発現する腫瘍があり、B7H3の発現はCCL2の発現およびM2マクロファージの量的な正の相関があり、B7H3の高い卵巣癌は、B7-H3の低い卵巣癌よりも腫瘍IFNγ+ CD8 + T細胞が少なく、予後が不良であった。したがって、腫瘍細胞におけるB7H3の発現は、CCL2-CCR2-M2マクロファージ軸を介した免疫抑制と腫瘍の進行に寄与すると考えます。これらの発見は、卵巣癌の腫瘍微小環境への新しい洞察を提供し、好ましくない卵巣癌の免疫抑制型の表現型に対する新しい治療アプローチの開発につながる可能性があります。